Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis
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The activation of NF-κB signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-κB pathway and Th cells homeostatis.
Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 μM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test.
In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibited the activation of NF-κB signaling pathway. Furthermore, DMB decreased interferon (IFN)-γ, increased IL-4 concentration in the mice splenocytes and the ratio of IgG1/IgG2a in the serum. In vitro, ROS production and pro-inflammation cytokines were markedly inhibited by DMB in RAW264.7 cell.
Our findings revealed that DMB alleviated mice colitis and inhibited the inflammatory responses by inhibiting NF-κB pathway and regulating the balance of Th cells.
KeywordsDMB Colitis NF-κB Th cell
Cortex Phellodendri Chinensis
Disease activity index
Hematoxylin and eosin
Inflammatory bowel diseases
Reactive oxygen species
Th cell type 1
Th cell type 2
Tumor necrosis factor-α
This work was supported by National Natural Science Foundation of China Grant 81573484 to Y.B.Z., Opening Project of Shanghai Key Laboratory of Complex Prescription (Shanghai University of Traditional Chinese Medicine) (14DZ2271000), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and College Students Innovation Project for the R&D of Novel Drugs (J1030830).
Compliance with ethical standards
Conflict of interest
There are no competing interests to declare.
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